Search PubMed⌕ Search

Biomedical subjects

S Govoni

Publications and source records attributed to S Govoni.

At least 199 records · Page 11Linked to original sources
PubMed1976

Effect of desmethyldiazepam and chlordesmethyldiazepam on 3',5'-cyclic guanosine monophosphate levels in rat cerebellum.

Three different ben,odia,epines (diazepam, its pharmacologically active metabolite desmethyldiazepam, and the derivative chlordesmethyldiazepam) have been compared in our study for their effects on 3',5'-guanosine monophosphate (cGMP) cerebellar levels. Desmethyldiazepam and chlordesmethyldiazepam are several-fold more potent than diazepam in decreasing rat cyclic cGMP cerebellar concentrations. None of the three drugs induces detectable changes of cerebellar cyclic 3',5'-adenosine monophosphate (cAMP). On the other hand, the three compounds did not modify the levels of cGMP in cerebellum of newborn rats, where Purkinje cell and dendrites lack synaptic contacts. However, injection of gamma aminobutyric acid (GABA) in the newborn is still able, as in the adult, to decrease cGMP concentration in cerebellum. Our data support the hypothesis that cGMP cerebellar concentrations may be reliable biochemical marker of the clinical activity of benzodiazepines.

Age Factors↗
PubMedDate not supplied

Neuropeptidergic inhibitory regulation of Met-enkephalin immunoreactive material release from rat spinal cord in vitro.

The release of Met-enkephalin immunoreactive material (ME-IR) from rat spinal slices was measured in vitro. This release increased about 4 fold in response to the addition of K+ ions. K+-evoked release of ME-IR was Ca++ dependent. Veratridine, a depolarizing agent, also stimulated the release of ME-IR. Veratridine-induced ME-IR release was completely prevented by tetrodotoxin (TTX), a Na+ channel blocker. Somatostatin (SRIF) inhibited both basal and K+-evoked release of ME-IR at 10(-7) M. Substance P had a similar effect although higher concentrations were needed. gamma-Aminobutyric acid (GABA) and neurotensin (NT) did not affect the basal release but slightly decreased K+-evoked release at 10(-5) M. Serotonin (5-HT) and noradrenaline (NA), did not affect ME-IR release. These results suggest that some of the neuropeptides present in the spinal cord, especially SP and SRIF, may be potent modulators of ME-IR release at the spinal level.

Animals↗
PubMedDate not supplied

Omegaconotoxin binding decreases in aged rat brain.

Omegaconotoxin binding was studied in young (3 months) and old (24 months) male Sprague-Dawley rats. In both groups omegaconotoxin binding displayed high affinity, was specific and saturable. The age-related changes are mainly a decrease in the Bmax in striatum and cortex (-29% and -31%, respectively). Binding parameters were unmodified in hippocampus of the two age groups. These data are consistent with the decrease of calcium uptake and neurotransmitter release observed in the brain of aged rodents.

Age Factors↗
PubMedDate not supplied

Regulation of phorbol ester binding and protein kinase C activity in aged rat brain.

Protein kinase C (PKC) function was analyzed in aged male Sprague-Dawley rat brain using two different approaches: the binding of [3H]-phorbol-12,13-dibutyrate and the in vitro phosphorylation of histone H1. In cortex the binding was decreased while in cerebellum no age-related modifications were observed. In hippocampus the binding capacity was increased in old animals and the affinity decreased. The kinase activity in both soluble and particulate fractions was decreased in cortex, increased in hippocampus and unmodified in cerebellum. The area selective, age-dependent modifications in neuronal PKC may sustain short- and long-term regional changes of neuronal excitability.

Age Factors↗
PubMedDate not supplied

Protein kinase C activity, translocation, and conventional isoforms in aging rat brain.

Protein kinase C was studied in various brain areas in aging Wistar rats. Histone-directed kinase activity from the cortex, hippocampus and cerebellum did not change with aging. Using purified protein B-50 as a substrate, between 3 and 8 months a decrease in in vitro phosphorylation was detected in the membrane fraction of the cortex but after this age values remained stable. In hippocampal membranes, B-50 phosphorylation was increased in aged rats. PKC translocation was impaired in aged rats in both the cortex and the hippocampus. PKC alpha and beta mRNA decreased in the cortex between 3 and 8 months with no further decline in aged animals. Hippocampal mRNA for calcium-dependent PKC isoforms was not modified during aging, as assessed by Northern and in situ hybridization. Western blot analysis revealed a change in PKC gamma protein only, which was increased in hippocampal membranes from aged rats. The data indicate that the key PKC function that is impaired in aged rats is enzyme translocation irrespective of the brain area investigated.

Aging↗
PubMedDate not supplied

Inositol 1,4,5-trisphosphate receptor and ryanodine receptor in the aging brain of Wistar rats.

Intracellular Ca2+ release channels are key players in the regulation of Ca2+ homeostasis. In the present study, we investigated the age-related changes of inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ release channel and ryanodine receptor/Ca2+ release channel in microsomes derived from either cerebellum or cerebrum cortex from male Wistar rats. A significant reduction (about 50%) in density of IP3 receptor/Ca2+ release channels was observed in cerebrum cortex, only, in 8- and 28-month old rats, whereas density and Kd of ryanodine binding sites were unaffected in both cerebellum and cerebrum microsomes. These findings, along with impairment of Ca(2+)-dependent protein kinase C phosphorylation of endogeneous substrates, point to coordinate, quantitative alterations of both targets of phosphoinositide metabolism, i.e., PKC and IP3 receptor, in the cerebrum cortex at least. The relevance of the present findings is discussed in relation to reported changes of neuronal Ca2+ homeostasis during aging.

Aging↗
PubMedDate not supplied

Calcium responses in human fibroblasts: a diagnostic molecular profile for Alzheimer's disease.

We have previously identified alterations of K+ channel function, IP3-mediated calcium release, and Cp20 (a memory-associated GTP binding protein) in fibroblasts from AD patients vs. controls. In the present study we introduce a scoring system based on these response alterations that integrates two or more alterations (and their degree) in AD vs. control fibroblasts. This scoring system generates an index that distinguishes AD patients from controls with both high specificity and sensitivity. We also show that low doses of bradykinin elicit intracellular calcium release almost exclusively in AD cell lines in an all or none fashion that provide a clear measurement of enhanced IP3-mediated function in AD vs. controls.

Aged↗